Peptide deformylase (DEF; EC 3.5.1.88) is a metallopeptidase that catalyzes the removal of an N-formyl group from N-formyl methionine, which is the initiating amino acid residue for prokaryotically translated proteins. DEF is an essential enzyme and mutations, deletions, or insertions in the DEF gene, or inhibition of enzymatic activity, are lethal to prokaryotic organisms. For decades DEF was believed to be exclusively restricted to prokaryotes because protein translation in eukaryotic organisms initiates with an unformylated methionine residue. The restriction to prokaryotic organisms and the essentiality of DEF have made this enzyme the molecular target of many research efforts directed towards the development of broad-spectrum antibiotics, which would have little or no mammalian toxicity. In 2000 the existence of DEF in the chloroplasts of higher plants was reported, and it was also discovered that actinonin, a potent inhibitor of DEF, was phytotoxic to all plant species. The lethality of actinonin to a wide range of plants, including many agriculturally significant weed species, suggests that DEF is an essential and highly conserved enzyme in plants, and inhibitors targeting this enzyme could potentially serve as a new class of broad-spectrum herbicides as well as selectable markers.
Accordingly, plant peptide deformylase (DEF) polypeptides provide an attractive target for crystallization and structural studies which can lead to the identification and synthesis of new broad-spectrum herbicides and selectable markers with high specificity towards plant DEF.